Novelty: Only six genes are used to diagnose and predict the reoccurrence of breast cancer versus 16 to 70 genes. Broadly applicable as the test is not specific to a certain type of breast cancer. The six gene model is also applicable to lung cancer and was tested in six lung cancer data sets. May also be applicable in other cancers

Clinical Application: Can be used when patients have been diagnosed with cancer to predict disease progression and, therefore, guide treatment decisions. A future application could also be to identify new therapeutics for breast cancer. Since it works in breast and lung cancer, the test has potential to work in other tumor types as well

General Description Several tests are available to help improve the prediction of patient survival upon diagnosis of breast cancer. These prognostic tests assist the decision-making process for cancer treatment by allowing physicians to identify patients who are at low risk of recurrence. The currently available tests examine the activity levels of 16 to 70 genes. NCI researchers have developed an assay for the diagnosis and prognosis of cancer patients that requires evaluating the activity levels of only six genes. The six gene signature they have identified is novel and independent of the genes used in the existing breast cancer prognostics and is broadly applicable to breast cancer rather than specific types or stages. The six-gene model has the same utility as those which measure the expression of a larger number of genes, but offers the advantage of being a more portable test because it allows for multiplexing which could possibly transform into a hospital-based test. The availability of this technology may also result in lower costs for the currently available, expensive assaysScientific Progress Using a mouse model of breast cancer, the inventors established a method to predict the outcome for human breast cancer patients by measuring the levels of six identified genes. The six gene test was then validated against publically available datasets obtained from previously conducted human clinical trials. In three datasets tested, there was a significant association between the six-gene model and relapse-free survival in two of the data sets (n = 159, P = 0.009; n = 179, P = 0.03) and overall survival in the third dataset (n = 176, P = 0.018). More recently, the 6-gene-model was validated for cancers other than breast using multiple, independent, publicly-available human lung cancer datasets. This technology has a potential use as a tool for cancer diagnosis and prognosis for breast, lung and potentially other cancer types. It also has potential as a cancer treatment target for therapeutic agents that are able to alter the activity of one of the six identified genesStrengths

Increased portability over currently available assays as it allows for multiplexing

Independently validated against three public data sets, independent of its training data sets

Novel gene signature, independent of those in currently available assays

May also have utility in cancer types other than breast

Weaknesses

The assay needs a comparative analysis with existing assays

All data has been obtained retrospectively. A prospective clinical validation is still needed

Testing a prognostic test in human subjects has some restrictions that could make meeting clinical endpoints difficult

Patent Status U.S. Patent Application No. 13/148,851, filed August 10, 2011; Google Patent Relevant Publication He, M.; et al. Clin Cancer Res, 2010, 16(1): 249-259 [PubMed ID: 20028755] Inventor Bios Steven K. Libutti, M.D., FACS Dr. Libutti is the Director of the Montefiore-Einstein Center for Cancer Care, Professor and Vice-Chairman of the Department of Surgery and Professor in the Department of Genetics at the Albert Einstein College of Medicine and the Montefiore Medical Center. He graduated from Harvard College and received his M.D. from the College of Physicians and Surgeons of Columbia University. Following his residency in Surgery, he completed a fellowship in Surgical Oncology and Endocrine Surgery at the National Cancer Institute (NCI) and was ultimately a tenured Senior Investigator and Chief of the Tumor Angiogenesis Section in the Surgery Branch, NCI. Dr. Libutti’s laboratory has focused on studies of the pathogenesis of neuroendocrine tumors and on the familial cancer syndromes MEN1 and vHL. His group developed some of the first mouse models of these conditions. Dr. Libutti has received funding from both the intramural and extramural programs of the NCI since 1996. He has published over 240 peer reviewed journal articles. He is the recipient of both NCI and NIH Director’s Awards. Dr. Libutti’s clinical interests are in endocrine and neuroendocrine tumors involving the thyroid, parathyroid, adrenal glands and pancreas. His laboratory developed some of the first genomics based diagnostic and prognostic assays for cancer. He is also a leader in regional cancer therapy and tumor targeted gene therapy. Dr. Libutti conducted the first clinical trial of tumor targeted colloidal gold nanoparticles in cancer patients. He has translated work from his laboratory to the clinic and currently holds seven US patents and has four patents pendingMei He, M.D. Dr. Mei He received her MD from Tianjin Medical University in China. She then worked as a Surgeon and Researcher in Tianjin Cancer Hospital and Cancer Research Institute. After relocating to the United Stage, she worked as a research associate in Dr. Edison Liu’s lab in Lineberger Comprehensive Cancer Center at University of North Carolina at Chapel Hill and later moved to the NIH with Dr. Liu where she worked as a Biologist and Lab manager. She focused on conducting and developing new experimental techniques in molecular biology research and detecting genetic alteration in breast cancer. She moved to Dr. Steven Libutti’s lab in the Surgery Branch within NCI where she was heavily involved in tumor angiogenesis studies; gene expression profiling; identification of gene signatures in human cancer; functional characterization of human genes and molecular biomarker for clinical screening and early diagnoses and prevention on cancer. Dr. He is currently working at NCI in the laboratory of Dr. Electron Kebebew. Her research interests include identification of candidate diagnostic and prognostic markers for endocrine malignancies; identification of novel classes of drugs with anticancer activity in thyroid cancer and adrenocortical carcinoma cells, then translating the findings into clinical trials, as well as clinical and genetic studies in familial non-medullary thyroid cancer. Some of her work has been published in over 30 peer reviewed journal articles and book chapters